This invention relates to wound dressings, in particular to dressings in fabric form and other forms suitable as contact layers for exuding wounds, and to methods for the manufacture of such dressings and of materials for use therein.
Commonly-used wound dressings include foams, sponges and fibre-based materials such as gauzes and waddings, for example of cotton or viscose rayon. Such fibre-based materials tend to adhere to the wound surface and are accordingly difficult to remove, after use, in one niece and without causing trauma to the patient. Known wound dressings also include advanced dressings based for example on alginates or on various kinds of hydrocolloids or hydrogels, but such dressings are relatively expensive and are accordingly used in general only when clinical needs so recommend. There exists a desire for wound dressings which possess at least some degree of absorbency, but which are sufficiently non-adherent that they are capable of being removed from a wound in a single piece without shedding fibre fragments and without trauma to the patient, and which are inexpensive in comparison with advanced dressings.
WO-A-94/16746 discloses a wound dressing in which the wound-contacting surface comprises carboxymethylcellulose (CMC) filaments capable of absorbing at least 15 times, preferably at least 25 times, their own weight of 0.9% by weight aqueous saline solution (as measured by a defined free-swell absorbency test) to form a swollen transparent gel, the thusly-swollen dressing retaining sufficient fibrous character to be removed as a coherent dressing from a wound. The degree of substitution (D.S.) of the CMC filaments is preferably at least 0.15, more preferably from 0.2 to 0.5, although it may be up to for example 1.0. The CMC filaments may generally be prepared by reacting cellulose filaments in the presence of strong alkali With chloracetic acid or a salt thereof. The cellulose filaments may be viscose rayon, cuprammonium rayon or cotton, but they are preferably solvent-spun and may accordingly be lyocell.
WO-A-95/19795 discloses a wound dressing which comprises a blend of textile fibres and gel-forming fibres. The textile fibres may be natural or synthetic but are preferably cellulosic fibres such as viscose rayon or cotton. The gel-forming fibres may for example be carboxymethylcellulose or alginate fibres. The gel-forming fibres can be of the type which retain their structural integrity on absorption of exudate or can be of the type which lose their fibrous form and become a structureless gel or a solution on absorption of exudate. The absorbency of the gel-forming fibre (measured by the free-swell method) is desirably at least 2 g/g of 0.9% saline solution, preferably at least 15 g/g, more preferably between 25 and 50 g/g. The D.S. of a carboxymethylcellulose fibre is desirably at least 0.05, preferably at least 0.2, more preferably between 0.3 and 0.5. Such dressings are said to have the advantage that the fibres they contain are not engulfed by new tissue formed during the healing process, so that they can he removed without causing wound injury.
According to a first aspect of the invention, there is provided a process for the manufacture of a wound dressing comprising the step of carboxymethylating a cellulosic fabric such that the absorbency (as defined hereinafter) of the fabric after carboxymethylation is no more than 3 g/g, preferably no more than 2.5 g/g, further preferably no more than 2 g/g or 1 g/g, greater than the absorbency (as defined hereinafter) of the fabric before carboxymethylation and such that the degree of substitution of cellulose by carboxymethyl groups in the carboxymethylated fabric measured by IR spectroscopy (as defined hereinafter) is in the range from 0.12 to 0.35, preferably from 0.2 to 0.3. The invention also includes wound dressings which comprise such carboxymethylated fabric.
By the absorbency of the fabric, before and after treatment, we mean the absorbency figures assessed by the method described in British Pharmacopoeia 1993, Addendum 1995, page 1706 for Alginate Dressings, but with substitution of the fabric under test for the alginate specified therein, which method yields absorbency in terms of weight per unit area, and then converted to absorbency in terms of weight ratio (g/g).
The cellulosic fabric preferably consists solely cellulosic fibre but may contain a proportion of non-cellulosic textile fibre or of gel-forming fibre. The cellulosic fibre is of known kind and may be a natural fibre such as cotton or a manmade fibre such as lyocell or viscose rayon; blends of such fibres may be used. We have observed that dressings according to the invention made from cellulosic fibres of low wet strength such as viscose rayon may tend to shed fragments when wetted, and accordingly use of such fibres is generally less preferred. The cellulosic fabric may comprise continuous filament yarn and/or staple fibre. A fabric of continuous filament yarn many be preferred, on the ground that such fabrics are less liable to shed fibre fragments on handling or on removal from a wound. We have nevertheless surprisingly found that dressings according to the invention composed of staple fibres have a low tendency to shed fragments.
The cellulosic fabric is of known kind and may be made in known manner. The basis weight of the fabric is generally in the range from 30 to 250 g/m2. The cellulosic fabric may be a woven or knitted fabric or a nonwoven fabric such as a hydroentangled fabric or a needlefelt. A nonwoven fabric should be of sufficiently robust constructionxe2x80x94for example, having sufficiently high fibre entanglementxe2x80x94that the carboxymethylated fabric after absorption of aqueous liquors possesses sufficient mechanical integrity to permit it to be removed from a wound in a single piece.
The carboxymethylation step is generally performed by contacting the fabric with strong alkali, for example sodium hydroxide, and a carboxymethylating agent such as chloracetic acid or a salt thereof such as the sodium salt. These reagents may be applied to the fabric separately or together. The reaction is conveniently performed in an aqueous system. This system preferably comprises a water-miscible organic solvent such as ethanol or industrial methylated spirit, in order to suppress swelling and dissolution of carboxymethylated cellulose. Reference may be made to WO-A-94/16746 for general discussion of the carboxymethylation reaction.
A preferred method of performing such a carboxymethylation step is as follows, and such a method of carboxymethylating a fibre of cellulose II forms a second aspect of the invention. Regenerated or reconstituted cellulose fibre (cellulose II) is contacted with a solution containing from 4 to 8 percent by weight sodium hydroxide, the amount of sodium chloracetate necessary to achieve the desired degree of substitution, from 50 to 60 percent by weight water, and the balance ethanol. For calculation purposes, the solution is considered to consist of the substances applied to the fibre and any moisture introduced with the fibre and/or ethanol. The solution may contain a small proportion of methanol if industrial methylated spirit is used as the source of ethanol. We have found that the presence of lower proportions of water than the specified minimum tends to result in uniform carboxymethylation, which is undesirable in the manufacture of dressings according to the invention. We have found that the presence of greater proportions of water than the specified maximum tends to result in too low a degree of reaction and too low a degree of slipperiness of the carboxymethylated fibre when wetted. We have further found that lesser proportions of water than those specified above are generally required for satisfactory results on fibres of cellulose I such as cotton. The method is preferably performed at from 40 to 80xc2x0 C., more preferably from 50 to 60xc2x0 C. The method is preferably performed for from 20 to 90 min., more preferably from 30 to 60 min. Ethanol may be substituted by another alcohol of the C1-C4 group. It will be appreciated that in general the more hydrophobic the alcohol, the lower the proportion of water that is desirable in the solution. Suitable proportions for alcohols other than ethanol can readily be determined by experiment. The method of the second aspect of the invention may be performed on loose fibre, yarn or fabric.
As explained hereinafter, it is thought that the large majority of the carboxymethyl groups in the carboxymethylated material according to the invention is located in the amorphous regions and that only a small minority is located in the crystalline regions. It is thought that the crystalline regions act as entanglement points in the polymeric structure, thus advantageously providing a fabric with good wet strength and also suppressing dissolution of carboxymethylcellulose. It is also thought that the relatively low absorbency is in part a consequence of this phenomenon; but it is one which does not detract from performance in the intended use. It will therefore be understood that severe carboxymethylation conditions, in particular the use of alkali at such a strength or temperature or for such a time that it converts the crystalline regions of cellulose to alkali cellulose thereby enabling reaction in the crystalline regions, are to be avoided.
According to a third aspect of the invention, there is provided a carboxymethylated cellulose article wherein the degree of substitution of cellulose groups measured by IR spectroscopy (as defined hereinafter) is in the range from 0.12 to 0.35, preferably from 0.15 to 0.3 or from 0.2 to 0.3, and wherein the degree of crystallinity measured by NMR (as defined hereinafter) is in the range from 10 to 70 percent, preferably from 15 to 60 or from 20 to 65 percent, more preferably from 30 to 55 percent. The article may take the form of a film, including a perforated film, a foam or sponge, or preferably a fibre. The invention also includes fabrics and dressings which comprise such articles. Wound dressings which comprise fibre according to the third aspect of the invention may conveniently be made by the process and method of the first and second aspects of the invention.
The 13C NMR spectrum of cellulose contains features in the 80-90 ppm region attributable to crystalline cellulose I and/or II. These features are essentially absent from the spectrum of fully carboxymethylated cellulose, such as that disclosed in WO-A-93/12275 and in WO-A-94/16746, and such material is accordingly thought to be amorphous. In contrast, spectra of carboxymethylated cellulose according to the third aspect of the invention exhibit these features to a significant extent, although generally at a somewhat lesser level than do spectra of cellulose I or II. This observation is consistent with the theory that the carboxymethyl groups are mainly located in amorphous rather than crystalline regions.
According to a fourth aspect of the invention, there is provided a method of carboxymethylating an article of cellulose II, wherein the article is contacted with a solution containing sodium hydroxide, sodium chloracetate, ethanol and water, characterised in that the weight ratio of sodium hydroxide to water is in the range from 0.095 to 0.115, preferably from 0.10 to 0.11, and in that the weight ratio of cellulose to water is in the range from 0.22 to 0.28, preferably from 0.24 to 0.26. The method is preferably performed at from 40 to 80xc2x0 C., more preferably from 50 to 60xc2x0 C. The method is preferably performed for from 20 to 90 min., more preferably from 30 to 60 min. It is thought that the sodium hydroxide concentration may correspond to a swelling maximum for cellulose. The article may be for example a fibre, an article containing a fibre such as a woven, knitted or nonwoven fabric, a film or a sponge. The amount of sodium chloracetate is chosen so as to achieve the desired degree of substitution. The amount of ethanol is chosen so as to achieve a suitable liquor-to-goods ratio. It will be appreciated that a high liquor-to-goods ratio is desirable for voluminous articles such as sponges and bulky nonwovens. Articles made by the method of the fourth aspect of the invention are useful in the manufacture of wound dressings, and the invention includes such dressings. The method of the fourth aspect of the invention can be used to make articles according to the third aspect of the invention.
A carboxymethylated fibre according to the third aspect of the invention made from lyocell or a carboxymethylated fibre made by the methods of the first, second or fourth aspects of the invention from lyocell may have an absorbency of at least 8 g/g of 0.9% (by weight) saline solution, as measured by the free swell method of WO-A-93/12275, and a tenacity of at least 10 cN/tex.
Upon wetting, a fabric dressing according to the invention retains its textile character, swells to a moderate degree and exhibits a desirable surface slipperiness or xe2x80x9cgel feelxe2x80x9d. We have surprisingly found in some cases that such a fabric dressing according to the invention may exhibit a lower absorbency than that of the cellulosic fabric, but that nevertheless when wetted it may exhibit a desirable degree of slipperiness (lubricity) when rubbed between the fingers. By way of guidance, a desirable degree of slipperiness in the present context is somewhat comparable to that observed when fingers wetted with weal, soap solution or with dilute aqueous alkali (e.g. 0.01-0.1M NaOH) are rubbed together. A dressing according to the invention which consists solely of carboxymethylated cellulose fibres has the advantage that it presents a homogeneous surface to the wound.
The dressings according to the invention may include or be used in conjunction with a secondary or backing layer of known type, for example an absorbent layer or a layer designed to maintain the wound environment, for example by keeping the wound moist. A backing layer may be affixed before or after the carboxymethylation step. Advantageously, the dressings of the invention may comprise a backing layer of a fusible thermoplastic fibre such as polypropylene, to permit thermal bonding to a further backing layer. Such a fusible backing layer may be incorporated in a fabric dressing by processes known in the manufacture of nonwoven fabrics such as needle bonding, stitchbonding and preferably hydroentanglement. The dressings according to the invention may be medicated. The dressings of the invention may comprise two or more plies of the fabric of the invention.
The dressings according to the invention find use particularly as coverings for exuding wounds, more particularly for chronic wounds.
IR Spectroscopy
The degree of substitution of cellulose air carboxymethyl groups (D.S.) was measured by IR spectroscopy as follows. IR spectra were recorded of viscose rayon (D.S. zero), of commercial samples of CMC of known D.S. (0.3, 0.6, 0.85 and 1.05), of a fabric made according to WO-A-94/16746 (D.S. 0.4), and of fabrics in accordance with the invention. Analysis of the spectra of the samples of known D.S. yielded the linear equation:
D.S.=0.678*I+0.05
where I is the ratio of the integrated peak intensity over the range 1600-1700 cmxe2x88x921 (Cxe2x95x90O stretch) to the integrated peak intensity over the range 1200-1000 cmxe2x88x921 (Cxe2x80x94O stretch). By D.S. in relation to the invention we mean the figure estimated using this equation.
The surface and bulk IR spectra of fabrics according to the invention were very similar. This suggests that carboxymethylation had taken place throughout the whole fibre rather than only in the surface regions.
The spectra of the fabric according to WO-A-94/16746 and of fabrics of the invention exhibited differences in detail: in particular, the shapes of the broad peak in the Oxe2x80x94H stretch region (3500-3000 cmxe2x88x921) differed, and the Cxe2x80x94O stretch region (1200-1000 cmxe2x88x921) of the fabric of the invention exhibited additional features. These differences could be seen most clearly from second-derivative spectra. The fabrics of the invention derived from rayon and lyocell exhibited sharp peaks at 3445 and 3480 cmxe2x88x921, attributable to crystalline cellulose II, whereas the sample according to WO-A-94/16746 did not.
NMR Spectroscopy
The degree of crystallinity of carboxymethylated cellulose was measured by NMR spectroscopy as follow. Solid state 13C NMR spectra were obtained at 75 MHz using a Bruker AC3000 (Trade Mark) spectrometer. Measurements were performed on samples packed into 7 mm zirconia rotors using proton-to-carbon cross-polarisation and magic angle spinning (CPMAS). Conditions employed were magic angle spinning speed of 5.0-5.5 kHz and a 90xc2x0 proton preparation pulse followed by 2 ms contact time with a pulse recycle time of 3 s. Typically, a thousand scans were acquired on each sample; this is a preferred minimum number. Intensity over the range 50 to 120 ppm was integrated, with background correction. Percentage crystallinity was calculated using the formula 100 (S-R)/S, where S is the integrated intensity of the sample under test and R is the integrated intensity of a reference sample of CMC prepared according to Example 1 of WO-A-94/16746.
Without wishing to be bound by theory, the results on articles according to the invention are consistent with substantially uniform carboxymethylation in the amorphous regions but little or no carboxymethylation in the crystalline regions. In contrast, the results on the fabric of WO-A-94/16746 are consistent with substantially uniform carboxymethylation of the whole fibre.